last updated April 2013
Defective protein causes fragile bones
International team determines key role of enzyme in bone formation
Using evidence from humans and zebrafish, biologists have linked the enzyme Bone morphogenetic protein 1 (BMP1) to the inherited bone fragility condition known as brittle-bone disease1. BMP1 plays a pivotal role in the maturation of Collagen I, the key ingredient of the extracellular matrix, which eventually mineralizes to become bone. Tom Carney of the Institute of Molecular and Cell Biology in Singapore and colleagues from Germany, Turkey and the US, found that BMP1 is not required for the generation or activity of the osteoblast cells which form bone. Rather, they showed that osteoblasts must produce functional BMP1 in order to generate the template for bone mineralization.
To identify the causative mutation, the researchers sequenced the gene coding portions of the genome of two related individuals with brittle bone disease from Turkey. The mutation, they discovered, was in the gene for BMP1. They then determined that the mutant BMP1 protein was neither stable nor secreted efficiently. As such, it showed a reduced capacity to modify Collagen I into its final active form. Mutation of the zebrafish Bmp1 gene corresponded to the zebrafish frilly fins mutant which displays similar bone defects. So, the researchers argue, the function of BMP1 is important enough to be conserved across a wide spectrum of vertebrate species.